title: Reproducibility of histological cell type in high-grade endometrial carcinoma.
abstract: Subclassification of endometrial carcinoma according to histological type shows variable interobserver agreement. The aim of this study was to assess specifically the interobserver agreement of histological type in high-grade endometrial carcinomas, recorded by gynecological pathologists from five academic centers across Canada. In a secondary aim, the agreement of consensus diagnosis with immunohistochemical marker combinations was assessed including six routine (TP53, CDKN2A (p16), ER, PGR, Ki67, and VIM) and six experimental immunohistochemical markers (PTEN, ARID1A, CTNNB1, IGF2BP3, HNF1B, and TFF3). The paired interobserver agreement ranged from κ 0.50 to 0.63 (median 0.58) and the intraobserver agreement from κ 0.49 to 0.67 (median 0.61). Consensus about histological type based on morphological assessment was reached in 72% of high-grade endometrial carcinomas. A seven-marker immunohistochemical panel differentiated FIGO grade 3 endometrioid from serous carcinoma with a 100% concordance rate compared with the consensus diagnosis. More practically, a three-marker panel including TP53, ER, and CDKN2A (p16) can aid in the differential diagnosis of FIGO grade 3 endometrioid from endometrial serous carcinoma. Our study demonstrates that the inter- and intraobserver reproducibility of histological type based on morphology alone are mostly moderate. Ancillary techniques such as immunohistochemical marker panels are likely needed to improve diagnostic reproducibility of histological types within high-grade endometrial carcinomas.
authors.affiliation: Department of Laboratory Medicine and Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
authors.forename: Guangming
authors.initials: G
authors.lastname: Han
authors.forename: Davinder
authors.initials: D
authors.lastname: Sidhu
authors.forename: Máire A
authors.initials: MA
authors.lastname: Duggan
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Arseneau
authors.forename: Matthew
authors.initials: M
authors.lastname: Cesari
authors.forename: Philip B
authors.initials: PB
authors.lastname: Clement
authors.forename: Carol A
authors.initials: CA
authors.lastname: Ewanowich
authors.forename: Steve E
authors.initials: SE
authors.lastname: Kalloger
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D018269:Carcinoma, Endometrioid / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000473:pathology; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D015588:Observer Variation; D015203:Reproducibility of Results; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor